Behavior is motivated by reward, and the most powerful rewards are those that satisfy a physiologic need. For decades, neuroscientists have studied the midbrain dopamine system to understand reward and hypothalamic circuits to understand sensing of internal needs. But how these two neural systems are interact to give rise to behaviors like eating and drinking remains poorly understood. Recently, we have used approaches for simultaneous neural recording and manipulation to observe directly the communication between these two systems. We have also mapped the signals they each receive from the gut in response to ingestion of food and fluids. This has revealed that hunger and thirst powerfully modulate the dopamine system, but do so in different ways and likely involve distinct circuit mechanisms. We propose here to build on these findings to systematically delineate how these neural circuits for need and reward interact in the brain.
In Aim 1, we investigate how these circuits represent internal needs, by recording their dynamics at multiple levels of analysis under different physiologic states, and further measuring how those dynamics are influenced by targeted circuit manipulations.
In Aim 2, we investigate how these circuits use information about bodily needs to drive learning about food, by monitoring and manipulating their activity during the learning process.
In Aim 3, we investigate how these circuits use information about internal state to drive motivation, by monitoring and manipulating their activity during tasks where animals must evaluate competing needs and rewards. These studies will provide fundamental insight into the mechanisms by which information about body needs is utilized by the brain to generate learning and motivation.
Eating and drinking are controlled by neural mechanisms in the brain that remain poorly understood. A better understanding of the structure and regulation of the underlying neural circuits would advance our ability to develop new therapeutic approaches for the treatment of medical conditions such as obesity and eating disorders. This proposal utilizes state-of-the-art approaches to selectively manipulate and record the activity of key neurons in the mammalian brain that influence eating and drinking.
